BRAINSTEM CELL DEATH AND SOMATOTROPIC PATTERN FORMATION

脑干细胞死亡和促生长模式形成

• 批准号: 6270267
• 负责人: MARK F JAQUIN
• 金额: $ 26.34万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-02-15 至 1999-02-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6270267
• 关键词: apoptosis; brain mapping; central neural pathway /tract; developmental neurobiology; ganglion cell; histology; laboratory rat; neurogenesis; neurotrophic factors; newborn animals; trigeminal nerve; vibrissae

Proposed studies will test the general hypothesis that whisker-related patterns (barrels) form in the brainstem, ahalamus and cerebral cortex as a direct consequence of spatiotemporally patterned, naturally occur=ring cell death in the trigeminal nucleus principalis that is regulated by the actions of neurotrophins on trigeminal ganglion cells. Anatomical, electrophysiological and morphometric methods will be applied to normal postnatal rats or postnatal rats that have received supplemental, exogenous nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and/or neurotrophin-3 (NT-3) during fetal intervals to answer the following questions: 1) Does the timecourse of naturally occuring cell death in nucleus principalis predict the timecourse of whisker-related pattern formation in nucleus principalis? 2) Are whisker-related patches in principalis produced by a patterned distribution of principalis cells and terminals that undergo naturally occurring apoptosis-like degeneration, therein producing inter-patch septae? 3) Does chronic augmentation of NGF, BDNF and /or NT-3 levels ameliorate naturally occurring cell death and affect pattern formation in principalis cells? 4) Under conditions that minimize principalis cell dath, do principalis cells develop normal dendritic trees; is the nucleus somatotopically organized; and is there a disproportionate number of cells with receptive fields on interwhisker surfaces? 5) Uner conditions that minimize principalis cell death, do principalis cells develop normal thalamic projections and do barrels develop in the cerebral cortex: These experiments therefore focus on the normal development of, and actions of neurotrophins upon, principalis cells, their thalamic projections and cortical representations. Studies addressing the normal development of, and actions of neurotrophins upon, trigeminal ganglion cells form a necessary foundation for this research and these experiments will be done in collaboration with other Program Project members (Drs. Andratde, Arends, Bennett-Clarke, Chiaia, Golden, Henderson, Johnson, Rhoades, Snider, Woolsey and Zahm). CORE "morphometry" and EM facilities will be employed. Neurotrophisn and their assays will be provided by Dr. E.M. Johnson and Regeneron. Proposed experiments may implicate general principles guiding somatosensory development in humans because of recent indications that humans have somatotopically parcellated, barrel-like aggregations in nucleus pri cipalis and the dorsal column nuclei (Noriega and Wall '91). In addition, biological actions of neurotrophic factors will be revealed that may be of future use in treating certain neuropathic disorders.

拟议中的研究将检验与胡须有关的一般假设， 模式（桶）形成在脑干，阿哈拉和大脑皮层， 时空模式的直接结果，自然发生=环 三叉神经主核的细胞死亡， 神经营养素对三叉神经节细胞的作用。 解剖学上， 电生理和形态测量方法将应用于正常 出生后大鼠或接受了补充的外源性 神经生长因子（NGF）、脑源性神经营养因子（BDNF）和/或 神经营养素-3（NT-3）在胎儿间隔期间回答以下问题 问题： 1)细胞核中自然发生的细胞死亡的时间进程 principalis预测了胡须相关图案形成的时间过程， 主核 2)在principalis中与胡须相关的斑块是由一种模式化的 主细胞和终末的分布， 发生类骨质疏松样变性，其中产生斑块间 隔膜？ 3)慢性增加NGF、BDNF和/或NT-3水平是否改善了 自然发生的细胞死亡和情感模式的形成 细胞？ 4)在使principalis cell dath最小化的条件下， 细胞发育正常的树突树;细胞核是体细胞定位的 有组织的;是否有不成比例的细胞与接受 晶须间表面的电场？ 5)在最小化主要细胞死亡的条件下， 细胞发育正常的丘脑投射，并且在丘脑中是否发育桶状突起 大脑皮层： 因此，这些实验的重点是正常的发展， 的神经营养因子，主要细胞，他们的丘脑投射， 皮质表征 关于正常发育的研究， 和神经营养因子的作用，三叉神经节细胞形成一个 为这项研究奠定必要的基础，并进行这些实验 与其他计划项目成员（Andratde，Arends， 贝内特-克拉克，奇亚，戈尔登，亨德森，约翰逊，罗兹，斯奈德， Woolsey和Zahm）。 将使用CORE“形态测定”和EM设备。 神经营养素及其测定将由Dr. E.M.提供。约翰逊和 Regeneron 拟议的实验可能涉及指导体感的一般原则 由于最近的迹象表明，人类有 在初级核内有躯体定位的包裹的桶状聚集体 （Noriega and Wall '91）。 此外，本发明还提供了一种方法， 神经营养因子的生物学作用将被揭示， 未来用于治疗某些神经性疾病。